Prevalence of metabolic syndrome in Chinese renal transplant ... - HKMJ

O R I G I N A L A R T I C L E

CY Cheung HW Chan YL Liu YH Chan HS Wong WL Chak KS Choi KF Chau CS Li

Prevalence of metabolic syndrome in Chinese renal transplant recipients

Objective To investigate the prevalence of metabolic syndrome in Chinese renal transplant recipients, using two different sets of diagnostic criteria.

Design Cross-sectional study.

Setting Regional hospital, Hong Kong.

Patients All Chinese patients who received solitary living–related or cadaveric kidney transplantation from 1 July 1997 to 31 December 2005 in our hospital with follow-up of more than 6 months were recruited. The diagnosis of metabolic syndrome was made according to the National Cholesterol Education Program–Adult Treatment Panel III (NCEP-ATPIII) criteria and the International Diabetes Federation criteria.

Results Using the modified (Asian) NCEP-ATPIII criteria, a total of 39 (32%) of 121 patients had metabolic syndrome, which included 20/69 (29%) of the males and 19/52 (37%) of the females. Using the International Diabetes Federation criteria, metabolic syndrome was diagnosed in 26% of the patients, 22% in males and 31% in females. In our patients, the most common component of metabolic syndrome was hypertension and the least common was low high-density-lipoprotein–cholesterol level. Low highdensity-lipoprotein–cholesterol levels were significantly more common in female patients.

Conclusion This study shows that there is a high prevalence of metabolic syndrome in our Chinese renal transplant recipients.

Introduction

Key words

Kidney transplantation; Metabolic syndrome; Prevalence Hong Kong Med J 2008;14:379-84 Renal Unit, Queen Elizabeth Hospital, 30 Gascoigne Road, Hong Kong CY Cheung, FHKCP, FHKAM (Medicine) HW Chan, FHKCP, FHKAM (Medicine) YL Liu, FHKCP, FHKAM (Medicine) YH Chan, FHKCP, FHKAM (Medicine) HS Wong, FHKCP, FHKAM (Medicine) WL Chak, FHKCP, FHKAM (Medicine) KS Choi, FHKCP, FHKAM (Medicine) KF Chau, FRCP, FHKAM (Medicine) CS Li, FRCP, FHKAM (Medicine)

The metabolic syndrome (MS) is a cluster of interrelated common clinical entities, which include: obesity, insulin resistance, glucose intolerance, hypertension, and dyslipidaemia. It has been well recognised that MS is closely associated with atherosclerotic cardiovascular disease in the general population.1 A community-based population study demonstrated that established cardiovascular disease risk factors are associated with the development of new-onset kidney disease.2 Moreover, among US adults, MS increases the risk of chronic kidney disease.3 Recently it has been found that MS is also common in renal transplant recipients.4 As in the general population, in renal transplant recipients, MS is associated with an increased risk of renal dysfunction and cardiovascular mortality.4-6 However, most of the published studies were based on Caucasians, there being a lack of data in Chinese renal transplant recipients. Interestingly, in the general population, the prevalence of MS differs widely among ethnic groups and according to the definition used.7-9 In the present study, we investigated the prevalence of MS in Chinese renal transplant recipients using different diagnostic criteria.

Methods Patients

This was a cross-sectional study. All Chinese patients who received solitary living–related or cadaveric kidney transplantation from 1 July 1997 to 31 December 2005 in Queen Elizabeth Hospital, Hong Kong with follow-up of more than 6 months were recruited. The study was Correspondence to: Dr CY Cheung performed in accordance with the Declaration of Helsinki. Written consent was obtained E-mail: [email protected] from each patient. Demographic and clinical data were extracted from patient records.

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2-hour postdose tacrolimus level; C4: 4-hour postdose tacrolimus level). Based on a previous pilot study in stable patients on tacrolimus in our centre, the AUC0-12 value was kept at around 100-150 ng x h/mL in the first 3 months and around 80-100 ng x h/mL thereafter.12 Since 2001, some of our patients did receive an interleukin-2 receptor antagonist during induction therapy; patients on cyclosporine were given basiliximab (Simulect, Novartis, Switzerland) while those on tacrolimus were given daclizumab (Zenapax, Roche, NJ, US). Basiliximab was given at a dose of 20 mg around 2-hour pre-transplantation and a second dose after 4 days. Daclizumab was given as a 1 mg/kg infusion around 2 hours before transplantation and then every 14 days for four doses. Acute rejection was defined as any episode with the relevant clinical and laboratory signs and symptoms and all such episodes were confirmed by renal biopsy. Our protocol for treating acute cellular rejection entailed 500 mg methylprednisolone given intravenously for 3 days. In case of steroid-resistant rejection, appropriate antibody therapy was started.

Measurements Immunosuppressive regimens Our patients were basically put on triple immunosuppressive therapy with either tacrolimus (Prograf, Astellas, Japan) or cyclosporine A (Neoral, Novartis, Switzerland), prednisolone and azathioprine. All patients received 500 mg of methylprednisolone at induction, followed by intravenous hydrocortisone 100 mg every 6 hours for 3 days and then oral prednisolone 30 mg daily. The dose of prednisolone was gradually tapered after the first month at a rate of 2.5 mg every 2 weeks and maintained at 7.5 mg daily. Azathioprine was given at a dose of 1.5 mg/kg daily since day 1 after the transplant. Cyclosporine was initially administered orally as a loading dose of 10 mg/kg within 12 hours of surgery and continued as 5 mg/kg twice daily. In this study, an abbreviated formula based on a limited sampling strategy was used to estimate the cyclosporine area under the 12hour concentration-time curve (AUC0-12). Calculation of cyclosporine AUC0-12 depended on the formula: 452.4 + C0 x 17.5 + C1.5 x 1.89 (C0: cyclosporine trough level; C1.5: 1.5-hour postdose cyclosporine level).10 The dose of cyclosporine was gradually titrated to maintain an abbreviated AUC0-12 of around 6000-8000 ng x h/mL in the first 3 months post-transplant, and 4000-6000 ng x h/mL thereafter.11 Tacrolimus was administered orally with a loading dose of 0.3 mg/kg within 12 hours of surgery and then 0.15 mg/kg twice daily. Abbreviated tacrolimus AUC0-12 monitoring was used. Calculation of tacrolimus AUC0-12 depended on the formula: 16.2 + C2 x 2.4 + C4 x 5.9 (C2:

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Subjects came back to our centre at 8:00 am after an 8-to-12–hour overnight fast. Fasting blood samples were drawn to determine serum creatinine, triglyceride, and high-density-lipoprotein (HDL) cholesterol and plasma glucose concentrations. Lowdensity-lipoprotein (LDL) cholesterol concentration was calculated using the Friedewald formula.13 Hypertension was defined as (i) the administration of antihypertensive agents and/or a history of this disorder; (ii) a systolic blood pressure greater than 130 mm Hg; or (iii) a diastolic blood pressure greater than 85 mm Hg. Weight, height, and waist circumference (midway between the iliac crest and the 10th rib) were also measured. Post-transplant diabetes mellitus (PTDM) was defined as a fasting blood glucose of more than 7 mM (126 mg/dL) on two occasions at any time after transplantation or associated with use of oral hypoglycaemic agents and/or insulin, in patients with no previous history of diabetes mellitus.

Diagnostic criteria for metabolic syndrome The diagnosis of MS was made according to the National Cholesterol Education Program–Adult Treatment Panel III (NCEP-ATPIII) criteria14 and the International Diabetes Federation (IDF) criteria.15 The five thresholds used were: (i) serum triglyceride level ≥1.69 mmol/L (≥150 mg/dL) or specific treatment for this lipid abnormality, (ii) serum HDL-cholesterol level 88 cm for women) were shown to be inappropriate for Asian Diabetes mellitus Pre-transplant 11 (28) 1 (1) 2.59 mmol/L (>100 mg/ dL); and (3) those with LDL levels ≤2.59 mmol/L (≤100 mg/dL), triglycerides levels >2.26 mmol/L (>200 mg/dL) and non-HDL cholesterol levels >3.36 mmol/L (>130 mg/ dL). They were all treated with lipid-lowering agents after failure of control with lifestyle modification.

In the present study, the diagnosis of MS was made according to the NCEP-ATPIII and IDF criteria, as they are easily applicable in a clinical setting and used widely. Our study showed that the prevalence of MS differed according to the criteria used, being slightly lower by IDF criteria (which recognises central obesity as an essential component). At present, there is no consensus on which diagnostic criteria for MS are best suited for renal transplant recipients. Further longitudinal studies of cardiovascular disease and renal allograft function are needed to clarify this issue. It has been reported that MS is a risk factor for renal dysfunction in the general population.2,3 In heart transplantation, Valantine et al30 suggested that a ‘metabolic milieu’ may modify the process of chronic transplant dysfunction. In longitudinal studies, de Vries et al4 and Porrini et al5 suggested that MS is associated with impaired renal allograft function. Different mechanisms have been proposed for the association between MS and impaired renal function. Obesity may contribute to renal dysfunction in many ways, such as excess excretory load, renal sodium retention, hyperinsulinaemia, insulin resistance, and renal lipotoxicity.31-34 Moreover, obesity is associated with worsening proteinuria in renal transplant recipients.18 Finally, glucose intolerance, hypertension and dyslipidaemia (all components of MS) directly damage the kidneys through renal or systemic atherosclerosis.35-38 Our series did not demonstrate a significant difference in renal function between patients with and without MS, probably because they were from a cross-sectional study and the sample size was small. In conclusion, the present study showed a high prevalence of MS in our Chinese renal transplant recipients, more so in females than males, and varied according to the different diagnostic criteria used. By the IDF criteria, which cites central obesity as an essential component, its prevalence was slightly lower.

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